Our MIT CCSB Tumor Cell Networks Center is directed tovrard achieving three overarching objectives: Objective 1 - Cancer Research: advance the development and application of new systems biology approaches to cancer research in three significant scientific areas (mitogenesis, migration, and DNA damage/repair) and improve corresponding approaches for discovery and use of cancer therapies; Objective 2 - Education: train a new generation of young research leaders comfortable at the interdisciplinary interface between experimental molecular/cell biology and quantitative modeling in key areas of basic and applied cancer research;Objective 3 - Collaboration and Outreach: serve the general cancer biology community by acting as a collaborative partner that brings new ideas and methods to a wide community of investigators regardless of institutional affiliation. A central thread integrating our experiment and modeling efforts is a paradigmatic 'cue-signal-response'framework for probing and modeling the regulation of tumor cell phenotypes critical to tumor cell biology. We aim to develop and make available to the cancer biology community successful models of three distinct but inter-related classes models: 'Cell Response'models, capable of predicting how cellular phenotypes are executed by biophysical molecular processes;'Signal-Response'models, capable of predicting how cellular responses are regulated by information carried by intracellular signaling pathways;and 'Cue-Signal'models, capable of predicting what intracellular signals are generated by environmental stimuli and therapeutic agents in the context of specific genotypes. The construction and testing of all three classes of models is currently underway and linked to three important problems in cancer biology and therapy: (a) cancer progression via dysregulation of mitogenic signaling pathways downstream of receptor tyrosine kinases;(b) cancer progression via inappropriate cell migration processes that promote invasive and metastatic behavior;and (c) cancer treatment via molecular pharmaceuticals including chemotherapeutics and targeted inhibitors. Our Education and Outreach activities include participation in regular meetings of a student/postdoc/faculty systems biology community at MIT as well as dedicated seminars and retreats,offering of curricular subjects, short courses, conference sessions, and symposia related to cancer systems biology. We also are proactive in making our data, models, and publications available on our website, and in collaborative interactions with cancer biology investigators at other institutions.